Epidemiologic Gladys

evidence

regarding

vitamin C and cancer1’2

Block Approximately 90 epidemiologic studies have the role ofvitamin C or vitamin-C-rich foods in cancer and the vast majority have found statistically sig-

ABSTRACT

examined prevention, nificant

protective

effects.

Evidence

is strong

for cancers

of the

oral cavity, stomach, and pancreas. There is also substantial evidence ofa protective effect in cancers ofthe cervix, rectum, and breast. Even in lung cancer, for which carotenoids show a consistent protective effect, there is recent evidence of a role for vitamin C. Vitamin C is an important antioxidant and free radical scavenger in plasma and acts to regenerate active vitamin E in lipid membranes. Although several different factors

indicated,

and

for illustrative

Oral,

in each cancer

one or two studies

site are described

purposes.

laryngeal,

and

esophageal

cancer

esophagus,

in fruits

and

vegetables

probably

act jointly,

the

and biochemical evidence indicate an important C. AmJClinNutr l99l;54:l3lOS-l4S.

KEY

WORDS

studies,

Ascorbic

cancer,

acid,

epidemiologic

role for vitamin

vitamin

C, epidemiologic

review

Graham

after

Vitamin C plays an important role in numerous biological systems. Its functions include synthesis of hormones, neurotransmitters,

collagen,

toxification

carnitine,

of exogenous (1-3).

and

In addition,

stituting

vitamin

E for

Immune

system

functions

to such

merous

studies

it plays

ascorbic

acid

or its derivatives

studies

in animal afford

membranes

(6,

prevention

7).

(8, 9). In ad-

metabolism,

to examine models,

the

as an antioxidant

shown

in normal

in the

de-

P-450

against lipid peroxiin sparing or recon-

of lipid

conducted

and

cytochrome

role

also been

functions

of experimental tumors reported in this issue. Epidemiologic

a major

have

been

substances,

and

it protects to function

protection

biological

have

other

compounds

and free radical scavenger and dation (4, 5). It has been shown

dition

the

nu-

role

of

or modulation

some

opportunity

of which to

are

examine

whether

established physiological or biochemical functions, or results from animal models, are borne out in human populations. Approximately 90 epidemiologic studies have been reviewed, comprising virtually all those that investigated the relationship between cancer incidence or mortality and either estimates of vitamin C intake or of fruits rich in vitamin C. For a detailed report of that review, see reference 10. Those results are summarized briefly here. For each cancer site the proportion of studies that produced statistically significantly protective results is 13 1OS

et al (13)

studied

374

patients

with

cancer

ofthe

larynx

and hospital control subjects. After control for possible confounding by alcohol intake and smoking, a low intake of vitamin C was associated with a risk ratio of 2.4 (P < 0.005). Offour studies that examined a vitamin C index in esophageal cancer (15-18), all found statistically significant relative risks of

Introduction

activity

Six of seven large, well-controlled studies found statistically significant risk associated with low intake of vitamin C or fruit. For example, McLaughlin et al (1 1) found those individuals in the lowest quartile of vitamin C intake had a risk ratio of 1.7 (men) or 2.0 (women). Winn et al (12) found those who reported consuming fruit once per week or less had 1.7 times the risk of those who consumed it seven times a week or more. Two of the studies also found protection from carotene-containing vegetables, whereas in the other studies evidence of protection from carotene was weaker or nonsignificant. Two studies of cancer of the larynx examined the role of vitamin C (13) or fruit (14), and both found significant effects.

Am J C/in Nuir

studies

for smoking

and

alcohol

consumption.

that

did

not

find

significant

protection

represented

such

population homogeneity ofintake that a protective effect would be impossible to detect. Among both cases and controls, few people ate fruit at least once a week. In summary, of eight studies that reported on a vitamin C index in cancer of the oral cavity, larynx, or esophagus, every one found a statistically significant elevation in risk associated with low intake. Three of these studies found carotene to be

I

From

Public

Health

Nutrition

Program,

School

University of California, Berkley. 2 Address reprint requests to 0 Block, 419 Warren ofCalifornia,

199 1 ;54: 1 3 105-145.

Downloaded from https://academic.oup.com/ajcn/article-abstract/54/6/1310S/4715249 by guest on 21 January 2018

adjustment

Brown et al (15) found that those in the lower third of the distribution for vitamin C intake had a statistically significant twofold risk ratio compared with those in the upper third. Fiber was also significantly protective, but carotenoids were not. Four studies that examined foods rather than nutrients found fruit or citrus fruit to be lower in cases. Dicarli et al (19) investigated the role of diet among 105 cases of esophageal cancer and hospital control subjects. After adjustment for alcohol, smoking, and other factors, only fruit intake remained strong (RR = 3.3) and statistically significant (trend P < 0.001). Three

Printed

Berkeley, in USA.

of Public

Health,

Hall, University

CA 94720. ©

199 1 American

Society

for Clinical

Nutrition

EPIDEMIOLOGIC

weak

and nonsignificant, whereas in two studies, vitamin A was found to be significant, but weaker than vitamin C. Of the

also

1 1 studies

of foods

significant

risk

did

not

intakes

report in both

populations, Lung

rather

for low

than

fruit

nutrients,

intake,

6 found

2 found

Pancreatic

statistically

suggestive

results

or

poor

treat

this

key

statistical significance, 2 found extremely low and control subjects in extremely high-risk and 1 found no effect.

tionnaire

not

designed

examined

7 found

in lung cancer in many cases

to assess

vitamin

the role of vitamin

statistically

Orleans

area.

significant

Results

vitamin

factor

C. Of

protection

were

adjusted

C intake

was

a statistically

appropriate multivariate cigarette smoking, and vitamin-supplement one-pack-a-day smoker with low dietary

from

high

in-

C intake

1253 lung cancontrols in the income,

a 25% chance whereas the

significant

pro-

adjustment for age, use. A 55-y-old male and supplemental vi-

ofdying from lung same smoker with

cancer in the 25high dietary and

vitamin C had only a 7% chance of lung cancer intake was also significantly and inversely related to subsequent lung cancer mortality, after age and smoking adjustment. Beta-carotene intake was not related to lung-cancer mortality.

Five recent

studies

ofdiet

protective

in lung cancer

effect

of vitamin

all found

C. Four

a statistically

of them

found

a

weak and nonsignificant effect offl-carotene; the fifth (22) found an equal effect of 3-carotene and vitamin C from foods in men and a stronger effect of f3-carotene in women. Of the 1 1 lung-cancer studies that specifically mentioned a vitamin

C score,

effect,

4 found

icant,

and

5 found

effects

2 reported

suggests

an important

tection,

the

pendent

recent

Pancreatic

significant

suggest

effect

that

direction

there

of vitamin

may

also

be an mdc-

C intake.

required version

relation

have

to either

jects in Louisiana. mg vitamin C/d,

examined

a vitamin 363

Compared those who

for

the

risk

C index

with higher cases and

risk of 2.6 for males, or < 0.05). Fruit consumption adjustment

heretofore

of pancreatic

or fruit,

intake. matched

with those consumed